Neurocognitive effects of methylphenidate on ADHD children with different DAT genotypes: A longitudinal open label trial

Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome "Tor Vergata", Via Alberico 2 n.35, 00193 Rome, Italy. Electronic address: .
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society (Impact Factor: 2.3). 03/2013; 17(4). DOI: 10.1016/j.ejpn.2013.02.002
Source: PubMed


The variable number of tandem repeat polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT) may influence the variability of the therapeutic response to methylphenidate (MPH) in Attention Deficit/Hyperactivity Disorder (ADHD). For this reason we evaluated the neuropsychological functioning after a prolonged period of MPH treatment and after a specific time from MPH suspension. Relationship between DAT VNTR genotypes and neurocognitive response to MPH was analyzed in a sample of 108 drug-naive ADHD patients. The performance of children with ADHD on measures of working memory, inhibition and planning was assessed at 4, 8 and 24 weeks and at 8 weeks after MPH withdrawal. Patients with 9/9 genotype evidenced an improvement in response inhibition and working memory only at 4 weeks of treatment, in planning at 24 weeks of therapy and after 8 weeks of MPH suspension. Patients with 9/10 showed an improvement in response inhibition at 4, 8 and 24 weeks of treatment, in planning at 24 weeks and after 8 weeks of MPH suspension. Patients with 10/10 evidenced an improvement in response inhibition and working memory at 4, 8 and 24 weeks of treatment and in planning at 4, 8 and 24 weeks of treatment and after 8 weeks of suspension. These results indicate that the 9/9 ADHD genotype has a different response at 24 weeks treatment with MPH. 10/10 DAT allele seems to be associated with an increased expression level of the dopamine transporter and seems to mediate the MPH treatment response in ADHD patients.

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    • "(2013), et al., 2005; Cummins et al., 2012), and reward-related striatal responsivity (Hahn et al., 2011; Hoogmann et al., 2013; Wittmann et al., 2013). In addition, DAT genotype is linked to how well a patient responds to psychostimulant treatment (Costa et al., 2013b; Gilbert et al., 2006; Kambeitz et al., 2013; Pasini et al., 2013). The DAT messenger RNA (mRNA) possesses a large, 3 0 untranslated region (UTR) that contains a variable number tandem repeat (VNTR) polymorphism (Vandenbergh et al., 1992a, 1992b) (Fig. 1). "
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